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Multinucleate giant cells release functionally unopposed matrix metalloproteinase-9 in vitro and in vivo.

Zhu XW, Price NM, Gilman RH, Recarvarren S, Friedland JS

Department of Infectious Diseases and Immunity, Imperial College London, Hammersmith Campus, London, W12 0NN, England.

Multinucleated giant cells (MGCs) are characteristic of granulomatous inflammation. Matrix metalloproteinase (MMP)-9, the major monocyte-derived matrix metalloproteinase, is key in inflammatory tissue damage. At 72 h, MGCs secrete 153 +/- 2.5 ng/mL MMP-9, compared with 115 +/- 3.8 ng/mL during macrophage differentiation (P<.05). In contrast, the level of MGC secretion-specific tissue inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1, is lower (P<.05). Mature MGCs secrete constitutively greater concentrations of MMP-9 than do monocytes or macrophages (P<.05). MGCs in tuberculous lymph-node biopsy samples express high MMP-9 levels adjacent to areas of necrosis, whereas TIMP-1 is not detected. Thus, MGCs are potentially important sources of MMP-9 secretion and may contribute to inflammatory tissue damage in human tuberculosis.

Published 31 August 2007 in J Infect Dis, 196(7): 1076-9.
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